Objective: Olaparib plus bevacizumab maintenance therapy improves survival outcomes in women with newly diagnosed, advanced, high-grade ovarian cancer with a deficiency in homologous recombination. We report data from the first year of routine homologous recombination deficiency testing in the National Health Service (NHS) in England, Wales, and Northern Ireland between April 2021 and April 2022.
Methods: The Myriad myChoice companion diagnostic was used to test DNA extracted from formalin-fixed, paraffin-embedded tumor tissue in women with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Tumors with homologous recombination deficiency were those with a BRCA1 / 2 mutation and/or a Genomic Instability Score (GIS) ≥42. Testing was coordinated by the NHS Genomic Laboratory Hub network.
Results: The myChoice assay was performed on 2829 tumors. Of these, 2474 (87%) and 2178 (77%) successfully underwent BRCA1/2 and GIS testing, respectively. All complete and partial assay failures occurred due to low tumor cellularity and/or low tumor DNA yield. 385 tumors (16%) contained a BRCA1/2 mutation and 814 (37%) had a GIS ≥42. Tumors with a GIS ≥42 were more likely to be BRCA1/2 wild-type (n=510) than BRCA 1/2 mutant (n=304). The distribution of GIS was bimodal, with BRCA1/2 mutant tumors having a higher mean score than BRCA1/2 wild-type tumors (61 vs 33, respectively, χ 2 test p<0.0001).
Conclusion: This is the largest real-world evaluation of homologous recombination deficiency testing in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is important to select tumor tissue with adequate tumor content and quality to reduce the risk of assay failure. The rapid uptake of testing across England, Wales, and Northern Ireland demonstrates the power of centralized NHS funding, center specialization, and the NHS Genomic Laboratory Hub network.
Competing Interests: Competing interests: RDM, BMB, HS, LY-S, YW, MV-P, RW, SM, SMc, EH, AG, SS, SN, SST and DGRE declare no conflicts of interest. KT is an employee and stockholder of Myriad Genetics, Inc. ARC declares research funding from AstraZeneca. SMac declares travel funding and speaker fees from AstraZeneca, Merck and Eli Lily. LT declares honoraria from AstraZeneca, Clovis Oncology, GSK and Tesaro. RM declares honoraria from AstraZeneca, Merck Sharp & Dohme and GSK and research funding from Barts & The London Charity, Rosetrees Trust, GSK and Yorkshire Cancer Research. JDB declares honoraria from AstraZeneca and GSK and consulting and advisory roles in Clovis Oncology and GSK. SB declares institutional grants from AstraZeneca and GSK, personal fees for speaker, consulting/advisory roles from Amgen, AstraZeneca, Clovis Oncology, Epsilogen, GSK, Immunogen, Mersana, Merck Sharp & Dohme, Merck Serono, Novartis, OncXerna, Pfizer, Roche, Shattuck Labs & Takeda. RSK declares honoraria from AstraZeneca, Clovis Oncology, GSK and Incyte and travel support from AstraZeneca, GSK and Sierra Oncology and trial grants from Merck Sharp & Dohme and consulting fees from Basilea Pharmaceutica and Shattuck Pharma. IMcN declares honoraria from AstraZeneca, Clovis Oncology, Epsila Bio, GSK, Roche and Scancell and institutional funding from AstraZeneca. JAL declares honoraria from AstraZeneca, Clovis Oncology, GSK, Eisai, Neopharm, Artios Pharma, Merck/Merck Sharp & Dohme, Mersana, Regeneron, VBL Therapeutics, Nuvation and Bristol Myers Squibb. GCJ declares research funding from AstraZeneca.
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